Polysaccharides having improved radiocontrast properties

Abstract

The present disclosure pertains to iodinated polysaccharide compounds that comprise a polysaccharide backbone that comprises a plurality of carboxyl groups and a plurality of iodinated side groups. The present disclosure also pertains iodinated polysaccharide compounds in which at least a portion of carboxyl groups that are present in a carboxyl-containing polysaccharide chain are functionalized with a plurality of iodinated side groups. Other aspects of the present disclosure pertain to methods of forming iodinated polysaccharide compounds, medical compositions comprising iodinated polysaccharide compounds, medical procedures comprising introducing such medical compositions into or between tissue of a patient, and medical kits that comprise such medical compositions.

What is claimed is: 
     
         1 . An iodinated polysaccharide compound that comprises a polysaccharide backbone that comprises a plurality of carboxyl groups and a plurality of iodinated side groups. 
     
     
         2 . The iodinated polysaccharide compound of  claim 1 , wherein the polysaccharide backbone comprises a carboxyl-containing polysaccharide chain to which the iodinated side groups are attached, the carboxyl-containing polysaccharide chain comprising one or more residues selected from one or more of glucuronic acid residues, mannuronic acid residues, or galacturonic acid residues. 
     
     
         3 . An iodinated polysaccharide compound in which at least a portion of carboxyl groups that are present in a carboxyl-containing polysaccharide chain are functionalized with a plurality of iodinated side groups. 
     
     
         4 . The iodinated polysaccharide compound of  claim 3 , wherein the carboxyl-containing polysaccharide chain comprises one or more residues selected from glucuronic acid residues, mannuronic acid residues, or galacturonic acid residues. 
     
     
         5 . The iodinated polysaccharide compound of  claim 1 , wherein the iodinated side groups comprise an iodinated aromatic group in which one or more hydrogens of an aromatic group is substituted by iodine and one or more hydrogens of the aromatic group is substituted by a hydrophilic group. 
     
     
         6 . The iodinated polysaccharide compound of  claim 5 , wherein the aromatic group is a phenyl group. 
     
     
         7 . The iodinated polysaccharide compound of  claim 1 , wherein the iodinated side groups comprise an iodinated aromatic group and a hydrophilic group. 
     
     
         8 . The iodinated polysaccharide compound of  claim 7 , wherein the iodinated aromatic side groups comprise a monoiodo-phenyl group, a diiodo-phenyl group, a triiodo-phenyl group or a tetraiodo-phenyl group. 
     
     
         9 . The iodinated polysaccharide compound of  claim 5 , where the hydrophilic group comprises a polyhydroxylated group. 
     
     
         10 . The iodinated polysaccharide compound of  claim 9 , wherein the polyhydroxylated group comprises a polyhydroxylated-C 1 -C 6 -alkyl-containing group. 
     
     
         11 . The iodinated polysaccharide compound of  claim 1 , wherein the iodinated side groups comprise a 2,4,6-triiodobenzene group in which at least one of the hydrogens at the 3 and 5 positions is substituted by a polyhydroxylated group. 
     
     
         12 . The iodinated polysaccharide compound of  claim 1 , wherein the iodinated side groups comprise an —N,N′-bis(polyhydroxy-C 1 -C 6 -alkyl)-2,4,6-triiodobenzene-3,5-dicarboxamide group. 
     
     
         13 . A method of forming the iodinated polysaccharide compound in accordance with  claim 1 , comprising forming an amide linkage by a coupling reaction in which an amino group of an amino-containing iodinated compound is reacted with carboxyl groups of the carboxyl-containing polysaccharide chain. 
     
     
         14 . The method of  claim 13 , wherein the coupling is performed in aqueous solution in the presence of a coupling agent. 
     
     
         15 . The method of  claim 14 , wherein the coupling agent is a carbodiimide coupling agent. 
     
     
         16 . The method of  claim 13 , wherein the amino-containing iodinated compound comprises an aromatic group in which one or more hydrogens is substituted by an amino-containing group, one or more hydrogens is substituted by iodine and one or more hydrogens is substituted by a hydrophilic group. 
     
     
         17 . A medical composition comprising the iodinated polysaccharide compound in accordance with  claim 1 . 
     
     
         18 . A medical procedure comprising introducing a medical composition of  claim 17  into or between tissue of a patient. 
     
     
         19 . The medical procedure of  claim 18 , further comprising imaging the medical composition using an x-ray-based imaging technique. 
     
     
         20 . The medical procedure of  claim 18 , wherein the medical procedure is selected from a procedure to implant a fiducial marker comprising the iodinated polysaccharide compound, a procedure to implant a tissue regeneration scaffold comprising the iodinated polysaccharide compound, a procedure to implant a tissue support comprising the iodinated polysaccharide compound, a procedure to implant a tissue bulking agent comprising the iodinated polysaccharide compound, a procedure to implant a therapeutic-agent-containing depot comprising the iodinated polysaccharide compound, a tissue augmentation procedure comprising implanting the medical composition, a procedure to introduce the medical composition between a first tissue and a second tissue to space the first tissue from the second tissue.